Women differ in their risk of developing breast cancer. Studies of individuals and families with exceptionally high risk have led to the identification of inherited breast cancer susceptibility genes, including BRCA1, BRCA2, p53, and recently, chk2. These and other cancer- predisposing genes were identified through studies of unusual patients with multiple primary cancers, early-onset cancers, precancerous lesions or cancers associated with malformation syndromes. Within this SPORE, the High Risk Core will identify patients at high risk of breast cancer who are likely to be informative in future cancer research. Our Core recruitment criteria include: families carrying one of the high penetrance breast cancer predisposing genes; early onset breast cancer particularly with a family history of either breast or ovarian cancer, family cluster of three or more first and second-degree relatives with either breast or ovarian cancer; breast cancer diagnosed before age 45 with family history of childhood cancers; breast cancer under 45, associated with major malformations or another primary cancer; or precancerous lesions (ADH, DCIS or LCIS) at any age. Our Core staff will consent eligible individuals and families to respond to a standard questionnaire and donate blood samples and their fresh or fixed tumor tissues for research. All tissue samples will be delivered to the Tissue and Pathology Core under Drs. Harris and Schnitt for processing, storage and future distribution. After replacing personal identifiers with codes, data on biospecimen availability and questionnaire information will be entered into a searchable database that can be accessed by approved SPORE investigators. Blood sample and tumor specimens will also be made available with approval. The High Risk Core will also facilitate re-contact of patients and families for additional collection of specimens and data, including mortality and the occurrences of new cancers on follow-up. Based on the proposed personnel, we will enroll at least 1,000 breast cancer cases over the next 5 years and at least 4,000 of their affected and at-risk relatives (total 5,000 family members).